DESCRIPTION: The hypothesis that forms the basis of this proposal is that expression of human hereditary cerebral hemorrhage with amyloidosis Dutch-type (HCHWA-D) mutant amyloid beta-protein precursor (ABPP) in the smooth muscle cells of cerebral blood vessels of transgenic mice will lead to cerebral amyloid angiopathy (CAA). The applicants plan to create transgenic mice that will express human ABPP carrying the HCHWA-D mutation in vascular smooth muscle cells in order to test the above hypothesis. Once they obtain positive transgenic mice, they will conduct specific immunohistochemical staining and immunoblotting studies on brain and other tissues from the transgenic mice to quantitatively and qualitatively determine the extent and distribution of human wild-type or HCHWA-D mutant ABPP protein expression. In addition, they will perform Northern blot analyses. Lastly, they will examine the transgenic mice for key pathological signs that are characteristic of CAA.